Neutron capture therapy is an attractive method for cancer therapy, specifically the treatment of malignant tumors. The generalized reaction involves capture of a thermalized neutron (usually from a nuclear reactor with special moderators and ports) by an appropriate nucleus having a large neutron capture cross section. The subsequent decay emits energetic particles (alpha particles) which can kill nearby tumor cells. Boron-10, for example, has such an appropriate nucleus and has particularly advantageous properties for this scheme. The boron-10/thermal neutron capture reaction is (asterisk indicating an unstable intermediate state of the Boron nucleus): EQU 10.sub.B +.sup.1 n.fwdarw.[.sup.11 B]*.fwdarw..sup.7 Li (0.87 Mev.)+.sup.4 He (1.52 Mev)
In order for this therapy to be effective, sufficient .sup.10 B must be localized in a tumor to generate the required density of particles. This level has been variously estimated to be approximately 10-50 ug.sup.10 B/gm tumor. Furthermore, the concentration of .sup.10 B in normal tissue and blood should be limited and preferably less than the concentration in tumor in order to minimize damage to healthy cells and blood vessels. H. Hatanaka (1986) Boron-Neutron Capture Therapy for Tumors; Nishimura Co., Ltd. p. 1-16.
Large numbers of boron-containing compounds have been tested for their ability to satisfy the above criteria. With few exceptions all have failed as not enough boron has localized in the tumor and the concentration in the blood has been too high for effective neutron capture therapy. Human clinical trials with Na.sub.2 B.sub.12 H.sub.11 SH in Japan have shown some promise, but only for a limited group of brain tumors. (gliomas) Id. 16-26.
Neutron capture therapy would be greatly expanded in usefulness if a generalized method for delivering high concentrations of .sup.10 B to tumors were available. It would further be useful if more .sup.10 B collected in tumor than in the blood. Recently, it has become possible to deliver drugs and other compounds selectively to tumors using liposomes of a particular composition and structure. See, for example, co-pending Vestar, Inc. patent application Ser. No. 674,201 entitled "Method of Targeting Tumors in Humans" which is incorporated herein by reference and which describes incorporation of radioactive agents at levels a million fold less than what is required for successful neutron capture therapy. Incorporation of compounds with higher osmolarity inside liposomes than outside, as is necessary for effective neutron capture therapy, has heretofore never been achieved and has been considered to be an unstable condition since the extra osmotic pressure should lead to breakage of the liposomes and/or leakage of the contents. Successful neutron capture therapy with liposomes depends on incorporating the highest concentration of .sup.10 B possible without substantially altering the liposome's favorable biodistribution characteristics. That can be accomplished by using compounds with the highest number of boron atoms practicable and by incorporating boron into liposomes at the highest possible concentration consistent with liposomes that are stable and target to tumors. It was found in the present invention that hyperosmotic solutions could be stably encapsulated while still maintaining good animal biodistribution performance. Thus the objective of at least 10 ug .sup.10 B per gram of tumor tissue could be met (assuming use of &gt;90% .sup.10 B enriched material). The present invention thus offers a method employing specially formulated liposomes, which encapsulate unexpectedly high concentrations of boron-containing compounds, and which collect in tumor tissue after intravenous injection or direct infusion into the artery that supplies the tumor. After a time to enable sufficient accumulation of boron-containing compounds in the tumor tissue, the subject can be subjected to a source that emits neutrons effective for neutron capture therapy.